Abstract
Data are accumulating that emphasize the important role of the intestinal barrier and intestinal permeability for health and disease. However, these terms are poorly defined, their assessment is a matter of debate, and their clinical significance is not clearly established. In the present review, current knowledge on mucosal barrier and its role in disease prevention and therapy is summarized. First, the relevant terms ‘intestinal barrier’ and ‘intestinal permeability’ are defined. Secondly, the key element of the intestinal barrier affecting permeability are described. This barrier represents a huge mucosal surface, where billions of bacteria face the largest immune system of our body. On the one hand, an intact intestinal barrier protects the human organism against invasion of microorganisms and toxins, on the other hand, this barrier must be open to absorb essential fluids and nutrients. Such opposing goals are achieved by a complex anatomical and functional structure the intestinal barrier consists of, the functional status of which is described by ‘intestinal permeability’. Third, the regulation of intestinal permeability by diet and bacteria is depicted. In particular, potential barrier disruptors such as hypoperfusion of the gut, infections and toxins, but also selected over-dosed nutrients, drugs, and other lifestyle factors have to be considered. In the fourth part, the means to assess intestinal permeability are presented and critically discussed. The means vary enormously and probably assess different functional components of the barrier. The barrier assessments are further hindered by the natural variability of this functional entity depending on species and genes as well as on diet and other environmental factors. In the final part, we discuss selected diseases associated with increased intestinal permeability such as critically illness, inflammatory bowel diseases, celiac disease, food allergy, irritable bowel syndrome, and – more recently recognized – obesity and metabolic diseases. All these diseases are characterized by inflammation that might be triggered by the translocation of luminal components into the host. In summary, intestinal permeability, which is a feature of intestinal barrier function, is increasingly recognized as being of relevance for health and disease, and therefore, this topic warrants more attention.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-014-0189-7) contains supplementary material, which is available to authorized users.
Highlights
Why do we need a gut barrier? The intestinal barrier covers a surface of about 400 m2 and requires approximately 40% of the body’s energy expenditure
Using TLR-4 mutant mice we showed that the onset of fructose-induced non-alcoholic fatty liver disease (NAFLD) is associated with intestinal bacterial overgrowth and increased intestinal permeability, subsequently leading to an endotoxin-dependent activation of hepatic Kupffer cells [104]
Apart from inflammatory bowel diseases (IBD), IBS, metabolic diseases and intestinal failure in critically ill patients, other diseases might be related to the gut microbiota and the intestinal barrier such as celiac disease [175,176], colon carcinoma [257] or inflammatory joint diseases [258]
Summary
Why do we need a gut barrier? The intestinal barrier covers a surface of about 400 m2 and requires approximately 40% of the body’s energy expenditure. Normal intestinal permeability Impaired intestinal permeability is a functional entity separating the gut lumen from the inner host, and consisting of mechanical elements (mucus, epithelial layer), humoral elements (defensins, IgA), immununological elements (lymphocytes, innate immune cells), muscular and neurological elements is defined as a functional feature of the intestinal barrier at given sites, measurable by analyzing flux rates across the intestinal wall as a whole or across wall components of defined molecules that are largely inert during the process and that can be adequately measured in these settings is defined as a stable permeability found in healthy individuals with no signs of intoxication, inflammation or impaired intestinal functions is defined as a disturbed permeability being non-transiently changed compared to the normal permeability leading to a loss of intestinal homeostasis, functional impairments and disease. Vitamins Vitamin A and its derivatives have been shown to regulate the growth and differentiation of intestinal cells, whereas vitamin A deficiency is associated with increased susceptibility to infection in both human and animal models [1]
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